Humanin suppresses receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation via AMP-activated protein kinase activation

• Published in: The Korean journal of physiology & pharmacology Vol. 23; no. 5; pp. 411 - 417
• Main Authors: Kang, Namju, Kim, Ki Woo, Shin, Dong Min
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Physiological Society and The Korean Society of Pharmacology 01.09.2019; 대한약리학회
• Subjects: Original; 약리학; Osteoclastogenesis; AMP-activated protein kinase; Receptor activator of nuclear factor-κB; ligand; Humanin
• ISSN: 1226-4512; 2093-3827
• DOI: 10.4196/kjpp.2019.23.5.411

Humanin (HN) is a mitochondrial peptide that exhibits cytoprotective actions against various stresses and diseases. HN has been shown to induce the phosphorylation of AMP-activated protein kinase (AMPK), which is a negative regulator of receptor activator of nuclear factor-κB ligand (RANKL). However, the role of HN in osteoclastogenesis or other skeletal disorders remains unknown. Here, we examined whether HN regulates osteoclastogenesis via AMPK activation using bone marrow-derived macrophage (BMM) cultures. Our results show that HN inhibited RANKL-induced osteoclast formation and reduced the expression of genes involved in osteoclastogenesis, including nuclear factor of activated T-cells cytoplasmic 1, osteoclast-associated receptor, cathepsin K, and tartrate-resistant acid phosphatase. Moreover, HN increased the levels of phosphorylated AMPK protein; compound C, an AMPK inhibitor, recovered HN-induced osteoclast differentiation. In addition, we found that HN significantly decreased the levels of RANKL-induced reactive oxygen species in BMMs. Therefore, these results indicate that HN plays an important role in osteoclastogenesis and may function as an inhibitor of bone disorders via AMPK activation.